Dr. Dragana Jankovic
NIAID, NIH
The current model of CD4+ T helper subsets is founded on both differentially expressed cytokines and the distinct functions mediated by these cytokines. It comprises the initially identified Th1 and Th2 effector cells as well as Th17 and Tfh lymphocytes (depicted with big circles). The complexity of Th lymphocytes responses in time (multistep maturation process) and place (various tissues) revealed additional but still poorly understood heterogeneity in the cytokine expression profiles of CD4+ T lymphocytes (small circles). Moreover, data from new technologies, such as fate-mapping and single-cell RNA sequencing, have added new complexity challenging the utility of the original cytokine-based Th nomenclature in understanding immune responses. Tuzlak et al. (1, 3) propose a new classification system for effector CD4+ T lymphocytes based on the type of help exerted and the nature of the cells engaged. Thus, in their nomenclature “type 1” helpers are those activating phagocytes, “type 2” helpers those stimulating B cells, eosinophils, mast cells and “type 3” those targeting stroma and epithelia. Jankovic et al. (2) argue that because individual Th effectors can affect the function of diverse hematopoietic or non-hematopoietic cell types and induce distinct but often opposing transcriptional programs in them, the classification proposed by Tuzlak and co-authors may be of limited applicability. They favor the retention of the original Th effector subset nomenclature based on cytokine profiling while expanding the concept to embrace the ever-evolving complexity of T helper immune responses.
- Tuzlak, S., Dejean, A.S., Iannacone, M. et al. Repositioning TH cell polarization from single cytokines to complex help. Nat Immunol 22, 1210–1217 (2021). https://doi.org/10.1038/s41590-021-01009-w
- Jankovic, D., Ciucci, T., Coffman, R.L. et al. Comment on: Repositioning TH cell polarization from single cytokines to complex help. Nat Immunol (2022). https://doi.org/10.1038/s41590-022-01144-y
- Tuzlak, S., Ginhoux, F., Korn, T. et al. Reply to ‘Comment on: Repositioning TH cell polarization from single cytokines to complex help’. Nat Immunol (2022). https://doi.org/10.1038/s41590-022-01142-0